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Selectins and selectin ligands in extravasation of cancer cells and organ selectivity of metastasis

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Abstract

Metastatic spreading is a dreadful complication of neoplastic diseases that is responsible for most deaths due to cancer. It consists in the formation of secondary neoplasms from cancer cells that have detached from the primary site. The formation of these secondary sites is not random and several clinical observations indicate that the metastatic colonization exhibits organ selectivity. This organ tropism relies mostly on the complementary adhesive interactions between the cancer cells and their microenvironment. In particular, several lines of evidence suggest that the organ selectivity of colon cancer cells for the liver involves the binding of the circulating cancer cells to endothelial E-selectin. The aim of this review is to make an integrative up-date of the mechanisms that govern the organ selectivity of the metastatic process focusing more especially on the role of selectins and selectin ligands.

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Abbreviations

CRP:

Complement regulatory protein

DR3:

Death receptor 3

ERK:

Extracellular signal-regulated kinase

MLC:

Myosin light chain

TNF:

Tumor necrosis factor

References

  1. Ribatti D, Mangialardi G, Vacca A (2006) Stephen Paget and the ‘seed and soil’ theory of metastatic dissemination. Clin Exp Med 6:145–149

    Article  PubMed  CAS  Google Scholar 

  2. Woodhouse EC, Chuaqui RF, Liotta LA (1997) General mechanisms of metastasis. Cancer 80:1529–1537

    Article  PubMed  CAS  Google Scholar 

  3. Chambers AF, Naumov GN, Varghese HJ et al (2001) Critical steps in hematogenous metastasis: an overview. Surg Oncol Clin N Am 10:243–255

    PubMed  CAS  Google Scholar 

  4. Mehlen P, Puisieux A (2006) Metastasis: a question of life or death. Nat Rev Cancer 6:449–58

    Article  PubMed  CAS  Google Scholar 

  5. Weiss L (1990) Metastatic inefficiency. Adv Cancer Res 54:159–211

    Article  PubMed  CAS  Google Scholar 

  6. Naumov GN, MacDonald IC, Weinmeister PM et al (2002) Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy. Cancer Res 62:2162–2168

    PubMed  CAS  Google Scholar 

  7. Cameron MD, Schmidt EE, Kerkvliet N et al (2000) Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer Res 60:2541–2546

    PubMed  CAS  Google Scholar 

  8. Luzzi KJ, MacDonald IC, Schmidt EE et al (1998) Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am J Pathol 153:865–873

    PubMed  CAS  Google Scholar 

  9. Paget D (1889) The distribution of secondary growths in cancer of the breast. Lancet 1:571–573

    Article  Google Scholar 

  10. Ewing J (1928) Neoplastic diseases. Saunders Edit, Philadelphia

    Google Scholar 

  11. Fidler IJ (1996) Critical determinants of melanoma metastasis. J Investig Dermatol Symp Proc 1:203–208

    PubMed  CAS  Google Scholar 

  12. Woltmann G, McNulty CA, Dewson G et al (2000) Interleukin-13 induces PSGL-1/P-selectin-dependent adhesion of eosinophils, but not neutrophils, to human umbilical vein endothelial cells under flow. Blood 95:3146–3152

    PubMed  CAS  Google Scholar 

  13. Laferriere J, Houle F, Huot J (2002) Regulation of the metastatic process by E-selectin and stress-activated protein kinase-2/p38. Ann N Y Acad Sci 973:562–572

    Article  PubMed  CAS  Google Scholar 

  14. Vestweber D, Blanks JE (1999) Mechanisms that regulate the function of the selectins and their ligands. Physiol Rev 79:181–213

    PubMed  CAS  Google Scholar 

  15. Kannagi R, Izawa M, Koike T et al (2004) Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis. Cancer Sci 95:377–384

    Article  PubMed  CAS  Google Scholar 

  16. Tremblay PL, Auger FA, Huot J (2006) Regulation of transendothelial migration of colon cancer cells by E-selectin-mediated activation of p38 and ERK MAP kinases. Oncogene 25:6563–6573

    Article  PubMed  CAS  Google Scholar 

  17. Hu Y, Kiely JM, Szente BE et al (2000) E-selectin-dependent signaling via the mitogen-activated protein kinase pathway in vascular endothelial cells. J Immunol 165:2142–2148

    PubMed  CAS  Google Scholar 

  18. Bird MI, Foster MR, Priest R et al (1997) Selectins: physiological and pathophysiological roles. Biochem Soc Trans 25:1199–1206

    PubMed  CAS  Google Scholar 

  19. Vestweber D, Blanks JE (1999) Mechanisms that regulate the function of the selectins and their ligands. Physiol Rev 79:181–213

    PubMed  CAS  Google Scholar 

  20. Brodt P, Fallavollita L, Bresalier RS et al (1997) Liver endothelial E-selectin mediates carcinoma cell adhesion and promotes liver metastasis. Int J Cancer 71:612–619

    Article  PubMed  CAS  Google Scholar 

  21. Witz IP (2006) The involvement of selectins and their ligands in tumor-progression. Immunol Lett 104:89–93

    Article  PubMed  CAS  Google Scholar 

  22. Sawada R, Tsuboi S, Fukuda M (1994) Differential E-selectin-dependent adhesion efficiency in sublines of a human colon cancer exhibiting distinct metastatic potentials. J Biol Chem 269:1425–1431

    PubMed  CAS  Google Scholar 

  23. Khatib AM, Fallavollita L, Wancewicz EV et al (2002) Inhibition of hepatic endothelial E-selectin expression by C-raf antisense oligonucleotides blocks colorectal carcinoma liver metastasis. Cancer Res 62:5393–5398

    PubMed  CAS  Google Scholar 

  24. Kobayashi K, Matsumoto S, Morishima T et al (2000) Cimetidine inhibits cancer cell adhesion to endothelial cells and prevents metastasis by blocking E-selectin expression. Cancer Res 60:3978–3984

    PubMed  CAS  Google Scholar 

  25. Mannori G, Santoro D, Carter L et al (1997) Inhibition of colon carcinoma cell lung colony formation by a soluble form of E-selectin. Am J Pathol 151:233–243

    PubMed  CAS  Google Scholar 

  26. Khatib AM, Kontogiannea M, Fallavollita L et al (1999) Rapid induction of cytokine and E-selectin expression in the liver in response to metastatic tumor cells. Cancer Res 59:1356–1361

    PubMed  CAS  Google Scholar 

  27. Nakamura S, Ohtani H, Watanabe Y et al (1993) In situ expression of the cell adhesion molecules in inflammatory bowel disease. Evidence of immunologic activation of vascular endothelial cells. Lab Invest 69:77–85

    PubMed  CAS  Google Scholar 

  28. Ye C, Kiriyama K, Mistuoka C et al (1995) Expression of E-selectin on endothelial cells of small veins in human colorectal cancer. Int J Cancer 61:455–460

    Article  PubMed  CAS  Google Scholar 

  29. Kakiuchi Y, Tsuji S, Tsujii M et al (2002) Cyclooxygenase-2 activity altered the cell-surface carbohydrate antigens on colon cancer cells and enhanced liver metastasis. Cancer Res 62:1567–1572

    PubMed  CAS  Google Scholar 

  30. Borsig L, Wong R, Feramisco J et al (2001) Heparin and cancer revisited: mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis. Proc Natl Acad Sci USA 98:3352–3357

    Article  PubMed  CAS  Google Scholar 

  31. Borsig L, Wong R, Hynes RO et al (2002) Synergistic effects of L- and P-selectin in facilitating tumor metastasis can involve non-mucin ligands and implicate leukocytes as enhancers of metastasis. Proc Natl Acad Sci USA 99:2193–2198

    Article  PubMed  CAS  Google Scholar 

  32. Peeters CF, Ruers TJ, Westphal JR et al (2005) Progressive loss of endothelial P-selectin expression with increasing malignancy in colorectal cancer. Lab Invest 85:248–256

    Article  PubMed  CAS  Google Scholar 

  33. Im JH, Fu W, Wang H et al (2004) Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation. Cancer Res 64:8613–8619

    Article  PubMed  CAS  Google Scholar 

  34. Biggerstaff JP, Seth N, Amirkhosravi A et al (1999) Soluble fibrin augments platelet/tumor cell adherence in vitro and in vivo, and enhances experimental metastasis. Clin Exp Metastasis 17:723–730

    Article  PubMed  CAS  Google Scholar 

  35. Fukuda M, Hiraoka N, Yeh JC (1999) C-type lectins and sialyl Lewis X oligosaccharides. Versatile roles in cell-cell interaction. J Cell Biol 147:467–470

    Article  PubMed  CAS  Google Scholar 

  36. Zipin A, Israeli-Amit M, Meshel T et al (2004) Tumor-microenvironment interactions: the fucose-generating FX enzyme controls adhesive properties of colorectal cancer cells. Cancer Res 64:6571–6578

    Article  PubMed  CAS  Google Scholar 

  37. Matsuura N, Narita T, Mitsuoka C et al (1997) Increased level of circulating adhesion molecules in the sera of breast cancer patients with distant metastases. Jpn J Clin Oncol 27:135–139

    Article  PubMed  CAS  Google Scholar 

  38. Ito K, Ye CL, Hibi K et al (2001) Paired tumor marker of soluble E-selectin and its ligand sialyl Lewis A in colorectal cancer. J Gastroenterol 36:823–829

    Article  PubMed  CAS  Google Scholar 

  39. Hakomori S, Kannagi R (1983) Glycosphingolipids as tumor-associated and differentiation markers. J Natl Cancer Inst 71:231–251

    PubMed  CAS  Google Scholar 

  40. Ogawa J, Inoue H, Koide S (1996) Expression of alpha-1,3-fucosyltransferase type IV and VII genes is related to poor prognosis in lung cancer. Cancer Res 56:325–329

    PubMed  CAS  Google Scholar 

  41. Seko A, Nagata K, Yonezawa S et al (2002) Down-regulation of Gal 3-O-sulfotransferase-2 (Gal3ST-2) expression in human colonic non-mucinous adenocarcinoma. Jpn J Cancer Res 93:507–515

    PubMed  CAS  Google Scholar 

  42. Ikeda N, Eguchi H, Nishihara S et al (2001) A remodeling system of the 3′-sulfo-Lewis a and 3′-sulfo-Lewis x epitopes. J Biol Chem 276:38588–38594

    Article  PubMed  CAS  Google Scholar 

  43. Lenter M, Levinovitz A, Isenmann S et al (1994) Monospecific and common glycoprotein ligands for E- and P-selectin on myeloid cells. J Cell Biol 125:471–81

    Article  PubMed  CAS  Google Scholar 

  44. Steegmaier M, Levinovitz A, Isenmann S et al (1995) The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor. Nature 373:615–20

    Article  PubMed  CAS  Google Scholar 

  45. Zou X, Shinde Patil VR, Dagia NM et al (2005) PSGL-1 derived from human neutrophils is a high-efficiency ligand for endothelium-expressed E-selectin under flow. Am J Physiol Cell Physiol 289: C415–424

    Article  PubMed  CAS  Google Scholar 

  46. Dimitroff CJ, Descheny L, Trujillo N et al (2005) Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells. Cancer Res 65:5750–5760

    Article  PubMed  CAS  Google Scholar 

  47. Gout S, Morin C, Houle F et al (2006) Death receptor-3, a new E-Selectin counter-receptor that confers migration and survival advantages to colon carcinoma cells by triggering p38 and ERK MAPK activation. Cancer Res 66:9117–9124

    Article  PubMed  CAS  Google Scholar 

  48. Napier SL, Healy ZR, Schnaar RL et al (2007) Selectin ligand expression regulates the initial vascular interactions of colon carcinoma cells: the roles of CD44V and alternative sialofucosylated selectin ligands. J Biol Chem 282:3433–3441

    Article  PubMed  CAS  Google Scholar 

  49. Tomlinson J, Wang JL, Barsky SH et al (2000) Human colon cancer cells express multiple glycoprotein ligands for E-selectin. Int J Oncol 16:347–353

    PubMed  CAS  Google Scholar 

  50. Mackay CR, Terpe HJ, Stauder R et al (1994) Expression and modulation of CD44 variant isoforms in humans. J Cell Biol 124:71–82

    Article  PubMed  CAS  Google Scholar 

  51. Aruffo A, Stamenkovic I, Melnick M et al (1990) CD44 is the principal cell surface receptor for hyaluronate. Cell 61:1303–1313

    Article  PubMed  CAS  Google Scholar 

  52. Haynes BF, Liao HX, Patton KL (1991) The transmembrane hyaluronate receptor (CD44): multiple functions, multiple forms. Cancer Cells 3:347–350

    PubMed  CAS  Google Scholar 

  53. Heider KH, Dammrich J, Skroch-Angel P et al (1993) Differential expression of CD44 splice variants in intestinal- and diffuse-type human gastric carcinomas and normal gastric mucosa. Cancer Res 53:4197–4203

    PubMed  CAS  Google Scholar 

  54. Rall CJ, Rustgi AK (1995) CD44 isoform expression in primary and metastatic pancreatic adenocarcinoma. Cancer Res 55:1831–1835

    PubMed  CAS  Google Scholar 

  55. Penno MB, August JT, Baylin SB et al (1994) Expression of CD44 in human lung tumors. Cancer Res 54:1381–1387

    PubMed  CAS  Google Scholar 

  56. Terpe HJ, Storkel S, Zimmer U et al (1996) Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor differentiation. Am J Pathol 148:453–463

    PubMed  CAS  Google Scholar 

  57. Reeder JA, Gotley DC, Walsh MD et al (1998) Expression of antisense CD44 variant 6 inhibits colorectal tumor metastasis and tumor growth in a wound environment. Cancer Res 58:3719–3726

    PubMed  CAS  Google Scholar 

  58. Hanley WD, Burdick MM, Konstantopoulos K et al (2005) CD44 on LS174T colon carcinoma cells possesses E-selectin ligand activity. Cancer Res 65:5812–5817

    Article  PubMed  CAS  Google Scholar 

  59. Burdick MM, Chu JT, Godar S et al (2006) HCELL is the major E- and L-selectin ligand expressed on LS174T colon carcinoma cells. J Biol Chem 281:13899–13905

    Article  PubMed  CAS  Google Scholar 

  60. Bodmer JL, Burns K, Schneider P et al (1997) TRAMP, a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas(Apo-1/CD95). Immunity 6:79–88

    Article  PubMed  CAS  Google Scholar 

  61. Chinnaiyan AM, O’Rourke K, Yu GL et al (1996) Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95. Science 274:990–992

    Article  PubMed  CAS  Google Scholar 

  62. Screaton GR, Xu XN, Olsen AL et al (1997) LARD: a new lymphoid-specific death domain containing receptor regulated by alternative pre-mRNA splicing. Proc Natl Acad Sci USA 94:4615–4619

    Article  PubMed  CAS  Google Scholar 

  63. Lohi O, Lehto VP (1998) ITAM motif in an apoptosis-receptor. Apoptosis 3:335–336

    Article  PubMed  CAS  Google Scholar 

  64. Laferriere J, Houle F, Taher MM et al (2001) Transendothelial migration of colon carcinoma cells requires expression of E-selectin by endothelial cells and activation of stress-activated protein kinase-2 (SAPK2/p38) in the tumor cells. J Biol Chem 276:33762–33772

    Article  PubMed  CAS  Google Scholar 

  65. Ohana-Malka O, Benharroch D, Isakov N et al (2003) Selectins and anti-CD15 (Lewis x/a) antibodies transmit activation signals in Hodgkin’s lymphoma-derived cell lines. Exp Hematol 31:1057–1065

    Article  PubMed  CAS  Google Scholar 

  66. Minn AJ, Gupta GP, Siegel PM et al (2005) Genes that mediate breast cancer metastasis to lung. Nature 436:518–524

    Article  PubMed  CAS  Google Scholar 

  67. Kaplan RN, Rafii S, Lyden D (2006) Preparing the “soil”: the premetastatic niche. Cancer Res 66:11089–11093

    Article  PubMed  CAS  Google Scholar 

  68. Hiratsuka S, Nakamura K, Iwai S et al (2002) MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2:289–300

    Article  PubMed  CAS  Google Scholar 

  69. Nicolson GL (1988) Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites. Biochim Biophys Acta 948:175–224

    PubMed  CAS  Google Scholar 

  70. Khatib AM, Auguste P, Fallavollita L et al (2005) Characterization of the host proinflammatory response to tumor cells during the initial stages of liver metastasis. Am J Pathol 167:749–759

    PubMed  CAS  Google Scholar 

  71. Haier J, Nicolson GL (2001) The role of tumor cell adhesion as an important factor in formation of distant colorectal metastasis. Dis Colon Rectum 44:876–884

    Article  PubMed  CAS  Google Scholar 

  72. Walzog B, Gaehtgens P (2000) Adhesion Molecules: The Path to a New Understanding of Acute Inflammation. News Physiol Sci 15:107–113

    PubMed  CAS  Google Scholar 

  73. Narita T, Kawakami-Kimura N, Kasai Y et al (1996) Induction of E-selectin expression on vascular endothelium by digestive system cancer cells. J Gastroenterol 31:299–301

    Article  PubMed  CAS  Google Scholar 

  74. Auguste P, Fallavollita L, Wang N et al (2007) The host inflammatory response promotes liver metastasis by increasing tumor cell arrest and extravasation. Am J Pathol 170:1781–1792

    Article  PubMed  Google Scholar 

  75. Wang HH, Qiu H, Qi K et al (2005) Current views concerning the influences of murine hepatic endothelial adhesive and cytotoxic properties on interactions between metastatic tumor cells and the liver. Comp Hepatol 4:8

    Google Scholar 

  76. Carrascal MT, Mendoza L, Valcarcel M et al (2003) Interleukin-18 binding protein reduces b16 melanoma hepatic metastasis by neutralizing adhesiveness and growth factors of sinusoidal endothelium. Cancer Res 63:491–497

    PubMed  CAS  Google Scholar 

  77. Kitakata H, Nemoto-Sasaki Y, Takahashi Y et al (2002) Essential roles of tumor necrosis factor receptor p55 in liver metastasis of intrasplenic administration of colon 26 cells. Cancer Res 62:6682–6687

    PubMed  CAS  Google Scholar 

  78. Araki M, Araki K, Biancone L et al (1997) The role of E-selectin for neutrophil activation and tumor metastasis in vivo. Leukemia 11(Suppl 3):209–212

    PubMed  Google Scholar 

  79. Gotsch U, Jager U, Dominis M et al (1994) Expression of P-selectin on endothelial cells is upregulated by LPS and TNF-alpha in vivo. Cell Adhes Commun 2:7–14

    Article  PubMed  CAS  Google Scholar 

  80. Kneuer C, Ehrhardt C, Radomski MW et al (2006) Selectins–potential pharmacological targets? Drug Discov Today 11:1034–1040

    Article  PubMed  CAS  Google Scholar 

  81. He XY, Xu Z, Melrose J et al (1998) Humanization and pharmacokinetics of a monoclonal antibody with specificity for both E- and P-selectin. J Immunol 160:1029–1035

    PubMed  CAS  Google Scholar 

  82. Hosono J, Narita T, Kimura N et al (1998) Involvement of adhesion molecules in metastasis of SW1990, human pancreatic cancer cells. J Surg Oncol 67:77–84

    Article  PubMed  CAS  Google Scholar 

  83. Nakashio T, Narita T, Sato M et al (1997) The association of metastasis with the expression of adhesion molecules in cell lines derived from human gastric cancer. Anticancer Res 17:293–299

    PubMed  CAS  Google Scholar 

  84. O I, Otvos L, Kieber-Emmons T et al (2002) Role of SA-Le(a) and E-selectin in metastasis assessed with peptide antagonist. Peptides 23:999–1010

    Google Scholar 

  85. Weston BW, Hiller KM, Mayben JP et al (1999) Expression of human alpha(1,3)fucosyltransferase antisense sequences inhibits selectin-mediated adhesion and liver metastasis of colon carcinoma cells. Cancer Res 59:2127–2135

    PubMed  CAS  Google Scholar 

  86. Matsumoto S, Imaeda Y, Umemoto S et al (2002) Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells. Br J Cancer 86:161–167

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by the Cancer Research Society Inc and the Canadian Cancer Society. SG holds a Post-Doctoral Fellowship from MEQ/FRSQ and PLT holds a PhD studentship from FRSQ.

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  1. Le Centre de recherche en cancérologie de l’Université Laval, L’Hôtel-Dieu de Québec, 9 rue McMahon, Quebec, Canada, G1R 2J6

    Stéphanie Gout, Pierre-Luc Tremblay & Jacques Huot

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  1. Stéphanie Gout
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  2. Pierre-Luc Tremblay
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  3. Jacques Huot
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Correspondence to Jacques Huot.

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Stéphanie Gout and Pierre-Luc Tremblay are co-first authors.

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Gout, S., Tremblay, PL. & Huot, J. Selectins and selectin ligands in extravasation of cancer cells and organ selectivity of metastasis. Clin Exp Metastasis 25, 335–344 (2008). https://doi.org/10.1007/s10585-007-9096-4

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